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Retinal layer thicknesses and neurodegeneration in early age-related macular degeneration: insights from the Coimbra Eye Study

  • Retinal Disorders
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Abstract

Purpose

This study aims to analyze the retinal layers and choroidal thickness in a large set of eyes with early age-related macular degeneration (AMD), in order to detect differences by stage suggestive of early neurodegeneration, and to explore biomarkers of different phenotypes.

Methods

This study is a population-based, cross-sectional study. Patients from the incidence AMD study (NCT02748824) with early AMD (Rotterdam 2a, 2b, 3) were included. All performed spectral-domain optical coherence tomography (SD-OCT) (Spectralis, Heidelberg Engineering, Germany) and automatic segmentation of all retinal layers was obtained with built-in software. Manual correction was performed whenever necessary. The mean thicknesses (ETDRS grid) and volume of each layer were recorded. Subfoveal choroidal thickness was manually measured. Estimates for each layer thickness were calculated with linear mixed models and tested for pairwise differences between stages. Associations between layer thickness and microstructural findings were assessed by multivariate regression analysis.

Results

The final cohort comprised 346 eyes (233 patients): 82.66% (n = 286) in stage 2a, 5.49% (n = 19) in stage 2b, and 11.85% (n = 41) in stage 3. A global tendency for lower/inferior thickness of the neuroretinal layers was found comparing stage 3 to 2a: retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) were inferior in the inner/outer ETDRS circles and the outer nuclear layer (ONL) and photoreceptors’ segments layer in the central circle (p ≤ 0.002). The retinal pigment epithelium–Bruch’s membrane (RPE/BrM) layer was thicker in stage 3 (p ≤ 0.001). Subretinal drusenoid deposits (SDD) were associated with thinner neuroretinal layers and choroid (p < 0.05).

Conclusions

Our results showed in a large population-based dataset that several inner and outer neuroretinal layers were thinner with a higher stage in early AMD. These findings support the existence of early and progressive neurodegeneration. Neuronal retinal layer thicknesses might thus be used as quantitative biomarkers of disease progression in AMD. The presence of SDD is possibly associated to more prominent and faster neurodegeneration.

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Acknowledgements

The authors thank Patricia Barreto and Maria Helena Madeira for their contribution in the development of the Coimbra Eye Study and in the epidemiological characterization of AMD in Portugal.

Funding

This study was an investigator-initiated study financially supported by Novartis.

Author information

Authors and Affiliations

  1. Association for Innovation and Biomedical Research on Light and Image (AIBILI), Coimbra, Portugal

    Cláudia Farinha, Rita Coimbra, Sandrina Nunes, Maria Luz Cachulo, João Pedro Marques, Isabel Pires, José Cunha-Vaz & Rufino Silva

  2. Department of Ophthalmology, Centro Hospitalar e Universitário de Coimbra (CHUC), Praceta Mota Pinto, 3000, Coimbra, Portugal

    Cláudia Farinha, Maria Luz Cachulo, João Pedro Marques, Isabel Pires & Rufino Silva

  3. Faculty of Medicine, University of Coimbra (FMUC), Coimbra, Portugal

    Cláudia Farinha, Ana Luísa Silva, Maria Luz Cachulo, João Pedro Marques, Isabel Pires, José Cunha-Vaz & Rufino Silva

  4. Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra (iCBR- FMUC), Coimbra, Portugal

    Rufino Silva

Authors
  1. Cláudia Farinha
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  2. Ana Luísa Silva
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  3. Rita Coimbra
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  4. Sandrina Nunes
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  5. Maria Luz Cachulo
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  8. José Cunha-Vaz
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  9. Rufino Silva
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Corresponding author

Correspondence to Cláudia Farinha.

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Ethics approval

All human-related procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Informed consent was obtained from all included participants

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The authors declare no competing interests.

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Farinha, C., Silva, A.L., Coimbra, R. et al. Retinal layer thicknesses and neurodegeneration in early age-related macular degeneration: insights from the Coimbra Eye Study. Graefes Arch Clin Exp Ophthalmol 259, 2545–2557 (2021). https://doi.org/10.1007/s00417-021-05140-0

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  • DOI: https://doi.org/10.1007/s00417-021-05140-0

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